Thoracic Insufficiency Syndrome (TIS) is the inability of the thorax to support normal respiration and normal postnatal lung growth. It represents a novel form of postnatal pulmonary hypoplasia and restrictive respiratory disease that occurs in children with congenital, infantile or neuromuscular scoliosis, congenital or acquired anomalies of the ribs and chest wall, and some skeletal dysplasias. While there is no standard treatment for TIS, Campbell and colleagues have reported the results of a series of children with congenital scoliosis and fused ribs treated with expansion thoracoplasty using a Vertical Expandable Prosthetic Titanium Rib (VEPTR) to directly address the thoracic hypoplasia from the fused ribs by lengthening the constricted hemithorax, and to indirectly address the associated scoliosis by distracting across the concavity of the curved spine. Their rationale for treatment was that in a growing child, removing the constriction on the lung and surgically enlarging the thorax would mechanically stretch the lung, resulting in both an increase in lung volumes and a compensatory increase in acinar development. While Campbell et al. have demonstrated accelerated thoracic vertebral growth and increased lung volume radiographically in children after expansion thoracoplasty, the impact of this procedure and the postnatal timing of the intervention on subsequent lung growth and lung compliance have not been described. Further, after removing the constrictive force on the lung, it is not known whether the lung parenchyma expands into areas that had already been open, or whether underdeveloped or underused (atelectatic) tissue is recruited. A clearer understanding of the relationships between expansion of the rib cage relative to the growth and development of the spine, ribs, and lung will provide a more targeted surgical protocol (including timing of the intervention) with more specific and predictable clinical outcomes. However, the fragile health of children afflicted with TIS makes it impossible to systematically evaluate the interdependence of growth of the spine, rib cage and lung in these individuals. Therefore, the goal of this R21 proposal is to extend an animal model of TIS previously developed by our Bgroup to quantify the effect of expansion thoracoplasty on the growth, development, and function of the spine, rib cage, and lungs. Specifically, two hypotheses will be evaluated: 1) TIS results from the prolonged mechanical inhibition of respiration and/or pulmonary growth;2) Reversal of thoracic constriction by expansion thoracoplasty at different postnatal ages will improve growth of the spine, rib cage, and lung in proportion to the growth potential remaining for these structures. PUBLIC HEALTH RELEVANCE: Thoracic Insufficiency Syndrome represents a novel form of respiratory disease that occurs in children with congenital or acquired anomalies of the ribs and spine. While there is no standard treatment, a new surgical procedure has been developed that addresses the chest and spine deformity by expanding the constricted rib cage, thereby allowing for improved lung function. A clearer understanding of the relationships between expansion of the rib cage relative to the growth and development of the spine, ribs, and lung will provide a more targeted surgical protocol (including timing of the intervention) with more specific and predictable clinical outcomes. A B